BioMarin Pharmaceutical Inc. ($BMRN)

Welcome to this fireside chat with BioMarin. It's my pleasure to host. I'm Joe Schwartz from the biopharma equity research team at Leerink Partners, and I'm pleased to be joined by Brian Mueller, Chief Financial Officer; and Cristin Hubbard, Chief Commercial Officer.

Thanks for joining us. Thanks for having us, Joe. Good morning.

Excited to be here.

So before we get into individual products, Brian, can you frame what's driving BioMarin's next phase of growth, particularly the mix of near-term commercial execution, upcoming pipeline milestones and portfolio expansion?

Yes, of course. Thank you, Joe. We're really excited about 2026 at BioMarin. We're coming off a strong performance year in 2025. We grew total revenues 13% in 2025. Within our business units, we grew our skeletal conditions business unit, which includes Voxzogo revenue at 26% last year and enzyme therapies at 9%. Looking ahead to this year and beyond, I think the way to frame it up, Joe, is there's three pillars to our corporate strategy: growth, innovation and value commitment. On the growth side, we're continuing to plan for strong growth from both of our business units. The midpoint of our guidance is high single digits for both skeletal conditions and enzyme therapies. We are also very excited and look forward to the assumed closing of the Amicus acquisition in Q2, which is going to bring two high-growth products into our commercial portfolio with an outstanding strategic fit in rare genetic conditions. On the innovation side, we're very excited to have a number of programs advancing. Just recently, we announced the approval of Palynziq in adolescents. I'm sure we'll get to it, and Cristin can elaborate on the opportunity there. We're expecting two Phase III data readouts this year, one in Voxzogo being examined in hypochondroplasia. This would be the second indication after the current approved indication of achondroplasia. And then BMN401 for ENPP1 deficiency. This asset came to us through the Inozyme acquisition last year. And then we're also advancing our additional clinical stage pipeline assets, BMN 351 for Duchenne muscular dystrophy, BMN333, which is BioMarin's long-acting CNP for achondroplasia, as well as our early-stage research programs. And then on the value commitment side, we transformed the company over the last couple of years with a significant focus on efficient cost allocations and disciplined expense management while growing the top line. This has led to leveraged growth. If you look through some of the special items in our 2025 P&L, we're growing earnings per share at the midpoint of our guidance at approximately 3x revenue. also looking to our third year of operating margin expansion and cash flow growth. So we're making great progress across all three pillars of the strategy, and we think creating a lot of value for shareholders.

Great. We appreciate that overview. So let's talk about Voxzogo. And I'm wondering since you're having such strong new patient starts and patients under age 2 now, how do you think about stickiness and whether -- I'm wondering if whether you have any strategies to forestall switching once new options become available and we have patients in multiple age segments? And how do you think about those dynamics?

Yes. And this is something that we've been doing a lot of thinking about, obviously. And first and foremost, I'd be the first to say that more options are great for patients. It certainly gives them the ability to choose what is right for them. And what we hear a lot of, Joe, is we're going out there and really understanding what today's market and the future market can look like is that at the end of the day, the decision makers for a switch are going to be the parents, the caregivers. Physicians tell us very often that they are there to provide any factual truths to lay out the options that are there. But at the end of the day, it's going to come down to that caregiver and that family and the decision that they choose to make for their child. So what we see in much of our market research in addition to the conversations that we're having is that for patients -- for the patients for whom there is efficacy that is being seen that that's going to be a high burden to switch. They've gotten used to their daily injections. They've gotten used to whatever the routine is. And so that we're seeing on average, about 2/3 of KOLs, physicians and caregiver research telling us that the chances of switch if the patient is doing well on therapy are low and not as compelling. So I think that really, at the end of the day, what it comes down to is efficacy matters, safety matters has over 10,000 patient years of that data to hold behind it, and then convenience comes third.

And that's really helpful. And as you look at the achondroplasia market, do you have a sense of how many patients are attracted to a value proposition, primarily based on growth and how many decision-makers view growth as a surrogate for other health benefits and how many individuals are just not interested in treating this condition?

Yes. And while I wouldn't say we have rigid numbers in terms of the buckets of specifically that, I will say that this landscape has evolved, and you would expect it to. Voxzogo was the first treatment ever available for achondroplasia hormone. And we're seeing this landscape evolve. As more data is being generated, as more publications are being made, we're certainly seeing there be more focus on the benefits beyond height. So AGV was, of course, what we had agreed to with the regulators, and that was the most visible sign of the product working. But at the end of the day, what is most compelling to families, to physicians, to those who treat achondroplasia is the broader health story, and that is precisely where we're building that body of evidence, and we're really moving the needle on that front.

Great. And can you talk a little bit more about that? What kind of efficacy on proportionality, if that's the right way to think about this, that there might be read-through from that? Obviously, BioMarin has the most experience of anyone in this space. So it would be great to hear some more about the strategy to communicate those benefits.

Yes. We've continued to publish, for instance, at SB in 2025. We've continued to publish our body of evidence and we are seeing areas such as for and magnum benefits. We are seeing symptomatic spinal stenosis benefits. We're certainly seeing proportionality where we have statistically significant data to show that proportionality is improved by treatment, including things like leg deformities, so tibial bowing, like any of the kind of various things that could affect their gait and their mobility at the end of the day, in addition to overall quality of health data, quality of life data, where you see also the kind of the more just overall life improvements and how they feel on the day-to-day. We're seeing all of these things benefit in our longer-term data, and we are continuing to publish on those and really share that story with physicians and families alike.

And just to add, this is an area where BioMarin will always be in the lead. We started our Voxzogo development program more than 15 years ago and we've got patients who have been on the therapy for 10 years now. The drug was approved in 2021. One, it was a conditional approval. One of the post-marketing commitments to file for full approval was this long-term data set where we followed a number of patients through final adult height. We now have that data, and we'll be filing it this year. And we'll see if that turns into something on a label amendment. But at a minimum, we're always -- and this is the level of publishing that Cristin mentioned, we're generating the longest and most robust data set.

Right. Okay. That makes sense. And then BMN 333 showed much more free CNP than Voxzogo. So I'd love to, as you embarked on a Phase II/III trial, discuss the strategy there to generate height as well as other health benefits. How much of a proportionality benefit or anything else do you think it would take to encourage patients to switch from Voxzogo or maybe one of the newer options to BMN 333.

Yes. Thanks, Joe. So our strategy with BMN 333, which I touched on is BioMarin's program for a long-acting CNP. However, it's really important to note that BMN 333 is not designed as just a convenience strategy. It's designed to be superior to Voxzogo and the competition based on the data we've seen. And to your question, we think that the Phase II/III seamless design study that we're enrolling will have the ability and the power to detect both the annualized growth velocity target as well as benefits beyond height. It's 120 patients designed to statistically detect a superiority to Voxzogo at the 90% level.

Okay. And switching gears to hypochondroplasia, the next potential opportunity for Voxzogo. How do your early indicators of market demand in hypochondroplasia compared to where you were at a similar stage of launch in achondroplasia?

So I'll start here. So we're really excited about being able to turn over the card and see the hypochondroplasia data coming up here soon in the first half of 2026. And the reason for that is that we have high confidence in the science. We saw really strong signals in Dr. Dauber's sponsored trial and therefore, are very much hoping to see that continue in our Phase III trial. Now importantly, when you asked the question about kind of what's the excitement around this, how do you see this playing out? I think the biggest and best proxy that we have to date in terms of the excitement around this indication is how quickly our Phase III trial enrolled. It went well beyond our expectations in terms of speed of enrollment, which oftentimes is a very good proxy for the excitement level. Now the work that we're doing today and the work that we think is very, very important for hypochondroplasia is in and around education and the diagnosis of this condition. While we believe the prevalence to be very similar to that of achondroplasia, we know that we have -- that we look at much lesser in terms of the -- or the TA, the total addressable patient population. And the reason for that is because it's not diagnosed at the rate that achondroplasia is. So we're doing a lot of our work today focused on disease awareness in addition to really figuring out how we can enhance the diagnosis journey and also shorten it because many of these patients are on average diagnosed around the age of 5 or 6. And similar to achondroplasia, we want to ensure that we're really getting patients treated as early as possible. So that diagnosis journey is very important.

And we hear that there's a wide or a fairly wide spectrum of severity in hypochondroplasia. And at the one end, the most severe end, some patients might already be on Voxzogo, but then we hear that there's some under the pope.

That they start to ask these questions in and around what might be happening, should we get a genetic test, et cetera. So that is specifically why we are so focused on ensuring that people understand some of those early signs of the condition and importantly, what that pathway to getting diagnosed can and should be. There are a significant proportion of these patients who would be eligible for treatment with Voxzogo, should those data turn out to be positive and importantly, in the way that we design the trial, a very significant proportion. But the bigger challenge is going to be ensuring that they are diagnosed early and that they are seen as eligible.

Okay. Great. And just one more question. Given we're almost halfway through the first half of the year, when is the hypochondroplasia Phase III data expected?

We have a few months left for the...

First half. Understood.

So stay tuned, Joe.

Great. We will, for sure. Okay. Great. Well, congratulations on the recent Amicus acquisition. It seems like a perfect fit for BioMarin. I guess to start, you've highlighted that Galafold is currently available in around 40 countries and BioMarin operates in around 80. So I'm wondering beyond simple geographic expansion, how much of the projected accretion in '27 relies on just deeper country penetration versus other dynamics?

Yes. So we are really excited about being able to say more as soon as we close, and we'll give far more detail at that point in time. But I think it's important to address your question specifically, we really do believe that there's the opportunity for both country expansion, given that, as you said, Joe, they're currently in 40 countries, and we have a larger country footprint of 80. But we also know there's opportunity for a deeper penetration in the markets in which Galafold already exists. And we say that because we know one of the biggest opportunities for Galafold and Fabry is really in and around diagnosis. And given that that's such a sweet spot for BioMarin to really be able to drive diagnosis of disease and then get those patients on therapy and have them stay adherent to said therapy, there's a big opportunity for both expansion into new countries and deeper penetration in the ones they're already in. And we're looking at those teams working diligently on and precisely what those plans will look like right now.

Gret. Yes. Thanks, Cristin. I'll just jump in, Joe, since you touched on accretion. I'll share that through these levers, again, subject to closing of the transaction, as we get deeper into the integration, we believe that there's opportunity to unlock even more value from Galafold and PomOp when we built our model to support the deal, of course, that's something that we have to have high confidence in to be able to make a share price bid and be confident in the value of the acquisition. What I mean by that is higher confidence usually means some base level of measured conservatism as well. So through these expansion opportunities, we think that we're actually going to be able to unlock more value over time. And Mike, in our comments at closing around accretion, which was, should we close the transaction in the second quarter of this year because we'll be incurring significant interest expense and just integrating the company, which comes with some cost, we think the transaction could be slightly dilutive in calendar '26, but accretive for its first 12 months and substantial accretion starting next year. And that's, again, based on that deal model. We'll say more upon closing, should, assuming we close.

Okay. Understood. Look forward to that. So Amicus on their own did a great job with Galafold and penetrated the amenable Fabry patients well. And it seemed like they were starting to get good traction with PomOp. And I'm just curious, at a high level, what kinds of operational does BioMarin bring to the table to take things to the next level for those kinds of products?

So I think very similar to what we just discussed with Galafold. I think that with PomOp, there's an even big opportunity. They're currently reimbursed in 15 countries and going back to the fact that we have a much larger country footprint, that's going to be an exciting opportunity out the gates. But I think what's really important, specifically for PomOp is the continual publication of real-world evidence that demonstrates the value of PomOp relative to those patients who have come off another enzyme therapy and Amicus has done a great job at starting to generate and publish those data, and that is something that we will very much look to continue so that you can generate a faster switch for those patients who are progressing in their disease.

It seems like there's a nice opportunity for PomOp. It's just getting started. And that takes me to my next question. Manufacturing has been a skill set that we associate with BioMarin doing in a really high-quality manner, and PomOp is a challenging product to manufacture. What is your plan on that front? I think they currently manufactured in China. They had talked about doing second source manufacturing has BioMarin settled on the strategy for manufacturing that product.

Thanks, Joe. I'll take that one. Yes, that question unfortunately falls into the category of we need to closed the transaction to be able to say more. During this period of time, it's really important that the two companies continue to operate as two independent entities. And there's some integration planning that we can do ahead of closing, but that level of deep integration with respect to manufacturing strategy is something they'll -- we'll have to wait to talk about. But the premise of your question is the right one which is that BioMarin is world-class manufacturing entity and we've got a great track record across our portfolio, both the commercial portfolio and the research and development portfolio of manufacturing globally and look forward to bringing that skill set to the Amicus asset.

Yes. Okay. That makes sense. Okay. So moving on, I guess we're looking forward to seeing the next data cut for BMN 351. And we have MDA going on now as we speak. Can you give us an update on what the next data cut will be for the first dose cohort and when we'll see data from the second dose cohort and what you hope to see there?

Yes. Thanks. So there's 3 doses, 6, 9 and 12 milligrams. So far, we've announced data from the 9-milligram dose at 26 weeks where we observed a mean dystrophin expression of 5%, so the key next data point will be watching the higher dose in the 12-milligram reach its next couple of milestones. But beyond dystrophin expression, we're also going to be looking at clinical benefits, which is really important in this community. We're doing both the North Star Ambulatory assessment, as well as forced vital capacity. So hopefully seeing a correlation between that dystrophin expression and the clinical benefits will be something else we're looking for.

And remind us of the threshold for you deciding to advance this program.

We're aiming for 10% dystrophin expression. But again, I would point to the clinical benefits that we're observing, and we'll look at the totality of the data to decide how to move forward.

Okay. Great. And let's touch on the Inozyme programs, given you have pivotal Phase III ENERGY-3 data expected also in the first half. Can you talk a little bit about what you hope to see on that front?

Yes. So we're, again, another program that we're very excited about and feeling very much that it fits right in the BioMarin sweet spot in rare disease, and that is really in being in a rare condition in ENPP1 deficiency where there is not otherwise a treatment. So we're very excited to see the pediatric data here coming up soon. And what we've estimated, and you can imagine the data are quite a wide range. But we believe that the total addressable patient population to be in and around 2,000 to 2,500 patients worldwide. And so our job, again, will really be to ensure that we can find those patients, get them diagnosed and get them on treatment as quickly as possible. Now as I said, this is just an estimate. As we found on the Naglazyme story back in the day was that you can estimate something. But then when there's a treatment available, it's amazing how much you learn about the condition and how many more patients and physicians are coming out to be -- are getting diagnosis because importantly, there is actually an option, which raises awareness. So we saw that quite a bit with the Naglazyme story. I don't know if you want to elucidate on that.

I will. Thanks, Cristin. It's -- this is a profound data point. I think, first of all, doing incidence, calculations in ultrarare disease as difficult as it is. But it is often the absence of a therapy that leaves these patients identified and once the therapy exists, with the improvement in diagnosis and disease awareness, you can really start to bring those patients in. You can look back at our 10-Ks on this. Naglazyme was approved approximately 20 years ago. And we used to cite global prevalence of the disease as 1,100 patients in existence. Here we are now 20 years later, we probably have almost 150% of that number actually on commercial there. So it's -- and again, this is what BioMarin does.

Still growing. Okay. Great. Well, maybe a couple of commercial -- more commercial questions to round out the discussion. I can't resist, but go back to Voxzogo. So can you discuss what underpins your assumption that Voxzogo revenues in the second half of this year are expected to be greater than the first half. Is that entirely due to OUS orders? I know there might be several moving parts because we might have the emergence of some competition. But can you just give us some insight into your crystal ball on that front?

Yes. Thanks, Joe. I'll take that one. So that timing, we shared on our Q4 '25 call that first of all, we'd see a similar lower first quarter as we did last year in 2025. And that for the full year, Voxzogo revenues would be weighted to both the back half generally and then even more specifically Q4. This is entirely order timing and largely international order timing. 75% roughly of Voxzogo's revenue is -- comes from outside the U.S. And most of those international customers are single national payer health care systems. So whether it be the way that their cash flows and budgeting works or their procurement model, we've observed this trend before where the purchasing patterns, again, across dozens of these countries just happens to be weighted to the second half of the year. What's really important to note and we point to this across all of our portfolio when we experience some of the -- some of this quarter-to-quarter volatility on revenue is that we've continually to steadily add patients quarter after quarter -- we expect that to be the case here in 2026. And so it really is just the timing that drives that dynamic.

Okay. Great. Well, that's helpful. Thank you so much for the update today. We look forward to following more progress at BioMarin.

Thank you, Joe.

I appreciate your time. Thank you.